Throughout the first half of the twentieth century there was a prevailing view that neurons within the vertebrate central nervous system (CNS) are electrically coupled at their synapses and that synaptic transmission therefore could only be mediated electrically.
About 1950 John Eccles and his colleagues realized that this could not be not true, and they were forced to conclude that synaptic transmission must be primarily a chemically mediated process. This realization stimulated research to identify the chemical messengers (neurotransmitters or transmitters). Electrophysiological experiments revealed that several amino acids either increased or decreased the excitability of neurons when applied to the extracellular surface.
The amino acids that increased neuronal excitability include glutamate, aspartate, cysteate, and homocysteate, which are all similar structurally. Those that decreased neuronal excitability include g-aminobutyric acid (GABA), glycine, b-alanine and taurine, which also exhibit structural similarity.
After the neuronal effects of these amino acids were reported, a debate arose as to whether these amino acids were really neurotransmitters or served some other undefined function in regulating or modulating the excitability of neurons. This debate is still not fully resolved, in part because there is not yet a precise understanding of all the chemical events that regulate neuronal excitability and their physiological significance.
Nevertheless, rigorous criteria have been developed that can be used to determine whether an amino acid is actually a neurotransmitter. Currently, three amino acids (glutamate, GABA, and glycine) meet the criteria sufficiently to allow a consensus conclusion that they are true neurotransmitters.
Furthermore, there is now little doubt that glutamate is the major excitatory neurotransmitter and that GABA and glycine are the major inhibitory neurotransmitters in the brain and spinal cord, respectively. Two more, aspartate and taurine, are likely to serve a significant, but as yet undefined, role in modulating the excitability of neurons.
A role for cysteate, homocysteate, and b-alanine is less certain.
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